A brain atlas of synapse protein lifetime across the mouse lifespan

Edita Bulovaite, Zhen Qiu, Maximilian Kratschke, Adrianna Zgraj, David G. Fricker, Eleanor J. Tuck, Ragini Gokhale, Babis Koniaris, Shekib A. Jami, Paula Merino-Serrais, Elodie Husi, Lorena Mendive-Tapia, Marc Vendrell, Thomas J. O’Dell, Javier DeFelipe, Noboru H. Komiyama, Anthony Holtmaat, Erik Fransén, Seth Grant (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
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Abstract

The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.
Original languageEnglish
Pages (from-to)4057-4073
Number of pages26
JournalNeuron
Volume110
Issue number24
Early online date5 Oct 2022
DOIs
Publication statusPublished - 21 Dec 2022

Keywords

  • synapse proteome
  • postsynaptic density
  • proteostasis
  • synaptome
  • protein turnover
  • aging
  • brain development
  • autism
  • dendritic spine
  • pyramidal neuron
  • HaloTag

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